Picolinic acid → 1,3-Bis(1,1-dimethylethyl) 2-(3-iodo-5-methylphenyl)propanedioate

Temperature

80 °C

Copper iodide (332 mg, 1.74 mmol), cesium carbonate (5.6 g, 17.4 mmol), and picolinic acid (429 mg, 3.49 mmol) were added to a dried flask under a nitrogen atmosphere. A solution of 3,5-diiodotoluene (3 g, 8.7 mmol) in dioxane (10 mL) was added, followed by the addition of di-tert-butyl malonate (1.3 mL, 8.7 mmol). The atmosphere inside the flask was removed under vacuum and replaced with nitrogen gas; this process was repeated a total of three times. The reaction mixture was then heated to 80° C. and stirred for 24 hours. The reaction mixture was then cooled to room temperature, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted twice with diethyl ether (50 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes to provide the title product as an orange oil (0.62 g).

1. customThe atmosphere inside the flask was removed under vacuum
2. temperatureThe reaction mixture was then cooled to room temperature
3. customquenched with saturated aqueous ammonium chloride solution (50 mL)
4. extractionextracted twice with diethyl ether (50 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by chromatography on silica gel
8. washeluted with ethyl acetate in hexanes

ORD record

ord-ede37bb8c27a4898a3ebfd9b5219c928

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895738B2